Presenting features and molecular genetics of primary hyperparathyroidism in the paediatric population

in European Journal of Endocrinology
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  • 1 Paediatric Unit, Blois General Hospital, Blois, France
  • 2 Epidemiology and Public Health Unit, Tours University Hospital, Tours, Centre, France
  • 3 Service de Néphrologie, Rhumatologie et Dermatologie Pédiatriques, Centre de Référence des Maladies Rares du Calcium et du Phosphore, Hôpital Femme Mère Enfant, INSERM UMR 1033, Bron, France
  • 4 Paediatric Unit, Montpellier University Hospital, Montpellier, Languedoc-Roussillon, France
  • 5 Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bicêtre Paris Saclay, Endocrinology and Diabetology for Children, Reference Centre for Rare Diseases of Calcium and Phosphate Metabolism, OSCAR Network, ERN BOND, Le Kremlin-Bicêtre, Toulouse, France
  • 6 Endocrine, Bone Diseases, and Genetics Unit, Reference Centre for Rare Diseases of Calcium and Phosphate Metabolism, OSCAR Network, ERN BOND, Children’s Hospital, Toulouse University Hospital, INSERM UMR 1043/CNRS 5828, Paul Sabatier University, Toulouse, France
  • 7 Paediatric Unit, Limoges University Hospital, Limoges, France
  • 8 Paediatric Unit, Nantes University Hospital, Nantes, Pays de la Loire, France
  • 9 Paediatric Unit, Bordeaux University Hospital, Bordeaux, Aquitaine, France
  • 10 Paediatric Unit, Amiens University Hospital, Amiens, Picardie, France
  • 11 Paediatric Unit, Brest University Hospital, Brest, Bretagne, France
  • 12 Endocrinology and Diabetology for Children, Necker University Hospital, AP-HP, Paris, Île-de-France, France
  • 13 Paediatric Endocrinology Unit, Lille University Hospital, Lille, Hauts-de-France, France
  • 14 Paediatric Unit, Poitiers University Hospital, Poitiers, France
  • 15 Paediatric Endocrinology Department, Angers University Hospital, Angers, Pays de la Loire, France
  • 16 Paediatric Unit, Rennes University Hospital, Rennes, Bretagne, France
  • 17 Paediatric Unit, Tours University Hospital, Tours, Centre, France
  • 18 Paediatric Unit, Besançon University Hospital, Besançon, France
  • 19 Paediatric Unit, Saint-Etienne University Hospital, Saint-Etienne, Rhône-Alpes, France
  • 20 Paediatric Unit, Strasbourg University Hospital, Strasbourg, Alsace, France
  • 21 Paediatric Unit, Reims University Hospital, Reims, Champagne-Ardenne, France
  • 22 Paediatric Unit, Lorient General Hospital, Lorient, France

Correspondence should be addressed to A Lienhardt-Roussie; Email: anne.lienhardt@chu-limoges.fr
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Aim

To describe the presenting features and molecular genetics of primary hyperparathyroidism (PHPT) in the paediatric population.

Methods

Retrospective study of 63 children diagnosed with primary PHPT from 1998 to 2018.

Results

Compared to older children, infants were often asymptomatic (54% vs 15%, P = 0.002) with a milder form of PHPT. When symptomatic, children and adolescents mostly presented with non-specific complaints such as asthenia, depression, weight loss, vomiting or abdominal pain. A genetic cause of PHPT was identified in about half of this cohort (52%). The infancy period was almost exclusively associated with mutation in genes involved in the calcium-sensing receptor (CaSR) signalling pathway (i.e. CaSR and AP2S1 genes, ‘CaSR group’; 94% of infants with mutations) whereas childhood and adolescence were associated with mutation in genes involved in parathyroid cell proliferation (i.e. MEN1, CDC73, CDKN1B and RET genes, ‘cell proliferation group’; 69% of children and adolescents with mutations). Although serum calcium levels did not differ between the two groups (P = 0.785), serum PTH levels and the urinary calcium/creatinine ratio were significantly higher in ‘cell proliferation group’ patients compared to those in the ‘CaSR group’ (P = 0.001 and 0.028, respectively).

Conclusion

Although far less common than in adults, PHPT can develop in children and is associated with significant morbidity. Consequently, this diagnosis should be considered in children with non-specific complaints and lead to monitoring of mineral homeostasis parameters. A genetic cause of PHPT can be identified in about half of these patients.

 

     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
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